A Study of SYH2069 Injection in Participants With T2DM Not Controlled With Diet/Exercise Alone or Metformin

A Multicenter, Randomized, Double-Blind, Placebo and Active Comparator-Controlled, Phase II Clinical Study to Evaluate the Efficacy and Safety of SYH2069 Injection in Participants With Type 2 Diabetes Mellitus With Inadquate Glycemic Control After Diet and Exercise Alone or Metformin Monotherapy

This study is a multicenter, randomized, double-blind, placebo and active-controlled, dose-finding phase 2 study aimed to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of SYH2069 Injection in participants with Type 2 Diabetes Mellitus (T2DM) inadequate glycemic control with diet and exercise alone or metformin monotherapy.

The study consists of four periods: a 2-week screening period, a 3-week run-in period, a 28-week treatment period and a 3-week safety follow-up period.

A total of 240 subjects will be enrolled. All subjects will be stratified by baseline HbA1c levels (≤8.5% or >8.5%) and prior metformin use (yes or no) , then randomized 4:1:4:1:4:1:4:1:4 to SYH2069 group 1, SYH2069 group 1 placebo, SYH2069 group 2, SYH2069 group 2 placebo, SYH2069 group 3, SYH2069 group 3 placebo, SYH2069 group 4, SYH2069 group 4 placebo and Tirzepatide injection 15mg, with 40 participants in each SYH2069 or Tirzepatide group and 10 participants in each SYH2069 placebo group. All treatment groups will implement dose titration to achieve the target dose.

Inclusion Criteria:

• 1. Male or female participants, 18-75 years of age.
• 2. Confirmed as T2DM for at least 12 weeks.
• 3. Body Mass Index (BMI): 22 kg/m^2 ≤ BMI ≤ 40 kg/m^2.
• 4. Treated with lifestyle intervention and stable treatment with metformin at least 8 weeks prior to screening.
• 5. HbA1c 7.5-10.5% (both inclusive) at screening visit.
• 6. Able to understand the protocol, and voluntarily signed informed consent.

Exclusion Criteria:

• 1. Type 1 diabetes or other specific types of diabetes.
• 2. Allergy to any active ingredient or any excipient of the investigational product, or presence of severe allergic diseases at screening.
• 3. Weight change >5% within 1 month before screening.
• 4. History of a level 3 hypoglycemic episode within 6 months prior to screening.
• 5. Acute complications of diabetes occurred within 6 months prior to screening.
• 6. History of severe chronic diabetic complications within 6 months prior to screening, or have non-proliferative diabetic retinopathy that requires treatment during the study.
• 7. History of acute or chronic pancreatitis.
• 8. History of acute cardiovascular and cerebrovascular within 6 months prior to screening.
• 9. History of malignancy of any organ system within 5 years prior to screening, excluding cured basal cell carcinoma and carcinoma in situ.
• 10. History or family history of medullary thyroid carcinoma (MTC), thyroid C-cell hyperplasia, or multiple endocrine neoplasia type 2 (MEN2).
• 11. History of major surgery or suffered blood loss of more than 400 mL within 3 months prior to screening.
• 12. Pregnant or lactating woman.
• 13. Other conditions judged by the investigator to be unsuitable for participation in this trial.